We describe the
gluten T-cell response of a DR7DQ2/DR9DQ9 heterozygous
celiac disease patient (CD555). Interestingly, this patient had T cells recognizing
gluten in the context of
human leukocyte antigen (HLA) molecules of both haplotypes. For the DR9DQ9 haplotype, DQ9 was identified as the
antigen-presenting molecule. As DQ9 carries
aspartate at DQ β57 but is otherwise identical to DQ8 and not considered associated with
celiac disease, we aimed to characterize this DQ9-restricted T-cell response in detail. By fractionation of
pepsin-
trypsin digested
gliadin we identified an
epitope stimulatory for several T-cell clones. This
epitope was identical to an
epitope (DQ8-glut-1) previously identified in DQ8 patients. In CD555, this was the dominant DQ9-restricted
epitope, whereas no T-cell response was found toward two other DQ8-restricted
epitopes. These findings correlated with
peptide binding data demonstrating that this
epitope bound better to DQ9 than the two other DQ8-restricted
epitopes. Although
glutamine to
glutamate exchange at P9 improved binding of all three
epitopes to DQ8, no such effect was observed for DQ9. The differential ability of DQ8 and DQ9 to harness a negatively charged anchor at P9 may result in fewer potential
gluten epitopes in DQ9 patients. Our data further indicate that DQ9 is a susceptibility factor for
celiac disease.